Renal plasma flow effective

Explain how plasma clearance of para-aminohippuric acid is used to determine the effective renal plasma flow... 

A substance that fulfills these criteria is para-aminohippuric acid (PAH). All of the PAH not filtered at the glomerulus is secreted by the proximal tubule. The net effect is that all of the plasma flowing through the nephrons is completely cleared of PAH. It is important to note that about 10 to 15% of the total renal plasma flow supplies regions of the kidneys that are not involved with filtration or secretion. Consequently, this plasma cannot be cleared of PAH. Therefore, the plasma clearance of PAH provides a measurement of the effective renal plasma flow, that is, the volume of plasma that actually flows through the nephrons. The ERPF is normally about 625 ml/ min. (This value is based on a renal blood flow of about 1.1 1/min and a hematocrit of about 42.)... 

To varying degrees, all inhaled anesthetics decrease glomerular filtration rate and effective renal plasma flow and increase filtration fraction. All the anesthetics tend to increase renal vascular resistance. Since renal blood flow decreases during general anesthesia in spite of well-maintained or even increased perfusion pressures, autoregulation of renal flow is probably impaired. 

GFR is estimated by calculating the clearance of the freely-filtered tracer or endogenous substance. RPF estimated using PAH clearance is often designated effective renal plasma flow (ERPF). Renal plasma flow is converted to renal blood flow (RBF) by dividing ERPF by the plasma fraction of whole blood, as estimated from the hematocrit (Hct) ... 

Davies DF, Shock NW. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest 1950 29 496-507. 

If a marker is extracted from the blood exclusively by the kidney resulting in a renal venous concentration of 0% (i.e. the arterio-venous extraction fraction is 100%), then the calculated value of the clearance of the marker (Cx) is equal to renal plasma flow. In practice, a compound, such as para-amino hippurate (PAH) with an extraction fraction of about 87%, is used. To acknowledge the fact that there is discrepancy between the PAH clearance and renal plasma flow, the term effective renal plasma flow is used when the extraction factor is not measured. In sum, renal plasma flow = effective renal plasma flow + extraction factor and renal blood flow = effective renal plasma flow + the hematocrit. 

In most studies in which it has been investigated, ethacrynic acid administration results in a marked reduction in renal vascular resistance [13, 19-21]. However, this effect is nullified, as in the case with furosemide, by the superimposition of volume depletion [20-22]- Studies of bumetanide in the experimental animal have generally shown no change in GFR or renal plasma flow (RPF) [23, 24] except for transient acute increases in the latter which approximated 27 to 40%, declining later in the experiments to only modest elevations or to control levels [25,26]. In man, bumetanide is associated with either no change [27,28] or a 12 to 16% increase in effective renal plasma flow and glomerular filtration rate [29]. 

ERPF effective renal plasma flow HIVAN HIVassociated nephropathy... 

Holdstock, N.B., Ousey, J.C. Rossdale, P.D. (1998) Glomerular filtration rate, effective renal plasma flow, blood pressure and pulse rate in the equine neonate during the first 10 days post partum. Equine Veterinary Journal, 30, 335-343. 

Indapamide did not significantly affect the function of patients with renal impairment and did not accumulate in the blood. In addition, the calculated half-life for indapamide in hypertensive hemodialysis patients is found to be very similar to the half-life observed in hypertensive patients with normal and compromised renal function (30). No adverse effect of indapamide on renal function is evident in normal volunteers, hypertensive patients or geriatric hypertensive patients after monitoring glomerular filtration rate or effective renal plasma flow (24). 

Spino M, Chai RP, Isles AF, et al. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis. J Pediatr 1985 107 64-70. 

PAH is an organic anion that has been used extensively for the quantitation of renal plasma flow. PAH is approximately 17% bound to plasma proteins and is eliminated extensively by active tubular secretion. Because PAH elimination is active, saturation of the transport processes have historically been anticipated, at concentrations of PAH in plasma above 10 to 20 mg/L. Recently, Dowling and associates used a sequential infusion technique and only observed concentration-dependent renal clearance of PAH at concentrations above 100 mg/dL. Furthermore, PAH is also metabolized, possibly within the kidney, to A-acetyl-PAH, and the analytical method must be able to differentiate the parent compound from the metabohte if one desires to obtain an accurate assessment of RPF. Prescott and coworkers noted that the renal clearance of PAH alone decreases at low plasma concentrations, while the clearance of the acetyl metabolite increases. Further studies are necessary to evaluate the mechanisms and significance of these findings. The extraction ratio (ER) for PAH is 70% to 90% at plasma concentrations of 10 to 20 mg/L, hence the term effective renal plasma flow (ERPF) has been used when the clearance of PAH is not corrected for the extraction ratio or if it is assumed to be 1. Normal values for ERPF are about 650 160 mL/min for men and 600 150 mL/min for women. Children will reach normahzed adult values by 3 years of age, and ERPE will begin to decline as a function of age after 30 years, reaching... 

Effective renal plasma flow (ERPE)—The flow of plasma through the kidneys often measured by para-amino hippurate (PAH) clearance and expressed in volume per unit of time (mL/min). The ERPF is less than the true renal plasma flow (RPF) because plasma flow through renal connective and adipose tissue is not measured and the extraction of PAH, although high (>0.9), is not complete. 

Effects of the drug on renal blood flow and glomerular filtration rate are related to alterations in extracellular fluid volume induced by the agent. PLarge doses (300 mg/day) have been reported to reduce effective renal plasma flow and glomerular filtration rate. 

The potassium-sparing agents, spironolactone, triamterene and amiloride appear to cause no consistent changes in RBF or glomerular filtration rate. However, when used in large doses, (300 mg per day or more), triamterene has been reported to reduce both effective renal plasma flow and glomerular filtration rale. Reductions in glomerular filtration rate have also been observed with spironolactone, but may have represented artifact related to chemical interference in the determination of sermn creatinine. 

Stoffel M, Jamar F, Van Nerom C, Verbruggen AM, Besse T, Squifflet JP, Beckers C (1996) Techne-tium-99m-L,L-ethylenedicysteine clearance and correlation with iodine-125 ort/zo-iodohippurate for determination of effective renal plasma flow. Eur J Nucl Med 23 365-370 Van Nerom CG, Bormans GM, De Roo MJ, Verbruggen AM (1993) First experience in healthy volunteers with technetium-99m L,L-ethylenedicysteine, a new renal imaging agent. Eur. J Nucl Med 20 738-746... 

The mechanism of excretion is predominantly based on renal tubular secretion. The TER of " Tc-MAG3 is 0.55 of the reference para-amino-hippurate ([PAH] 1.0) in comparison, orf/io-iodohippurate (OlH) shows a value of 0.83 (Bubeck et al. 1987). Using this coefficient (0.55), Tc-MAG3 may substitute for OlH as an indicator of effective renal plasma flow (ERPF) (Bubeck et al. 1990). 

A study in 16 healthy subjects found that indometacin 100 mg twice daily for 9 days reduced the maximum blood levels of a single 300-mg dose of ciclosporin by 18% and slowed its absorption (time to maximum concentration increased by 30 minutes) but the extent of absorption was not changed, indicating the absence of a clinically relevant pharmacokinetic interaction. Further, the pharmacokinetics of indometacin were not affected by ciclosporin. A study in rheumatoid arthritis patients taking ciclosporin 2.5 mg/kg daily, found that creatinine clearances were reduced by 6% in those taking indometacin 50 mg four times daily, but this was not considered to be clinically important. An experimental study in healthy subjects found that ciclosporin 10 mg/kg twice daily for 4 days had no effect on effective renal plasma flow (ERPF) or the glomerular filtration rate (GFR), but when indometacin 50 mg twice daily was added the ERPF fell by 32% and the GFR by 37%. ... 

PAH is secreted into the tubules on a single pass, and 10%-15% of the RPF goes to nonfiltering portions of the kidney. This nonfiltered plasma cannot therefore lose its PAH, and thus PAH clearance = effective renal plasma flow = 0.5%-90% of total RPF. 

An indirect measurement of RBF can be made using para-aminohippuric acid (PAH) clearance. This molecule is an ideal marker of the effective renal plasma flow (eRPF), as it freely filters through the glomerulus, and any amotmt remaining in the peritubular capillary plasma is secreted into the proximal tubule. Therefore, essentially aU PAH passing through the kidneys appears in the urine. For this reason, the PAH clearance is directly proportional to the rate of plasma flow through the kidneys. If the hematocrit is known, the total renal blood flow can be easily calculated from the eRPF value. 

Laroute V, Lefebvre HP, Costes G, Toutain PL (1999) Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and p-aminohippuric acid. J Pharmacol Toxicol Methods 41 17-25 LeBel CP, Foss JA (1996) Use of a rodent neurotoxicity screening battery in the preclinical safety assessment of recombinant-methionyl human brain-derived neurotrophic factor. Neurotoxicology 17 851-863... 

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